(7S,8aR)-1,2,3,4,6,7,8,8a-octahydropyrrolo[1,2-a]pyrazin-7-ol

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To (7S,8aR)-octahydropyrrolo[1,2-a]pyrazin-7-ol (0.208 g, 1.463 mmol) and 4-(trifluoromethyl)benzene-1-sulfonyl chloride (0.358 g, 1.463 mmol) in dichloromethane (3 mL) was added triethylamine (303 mg, 3 mmol). The mixture was stirred at room temperature overnight. The mixture was concentrated and the residue was purified by chromatography on silica gel (CH2Cl2/CH3OH=10:1) to give the title compound (0.4 g, 78% yield). MS (ESI) m/z 421 (M+H)+. The mixture was concentrated the residue was purified by chromatography on silica gel (CH2Cl2/CH3OH=10:1)

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To (7S,8aR)-octahydropyrrolo[1,2-a]pyrazin-7-ol (0.208 g, 1.463 mmol) and 4-(trifluoromethyl)benzene-1-sulfonyl chloride (0.358 g, 1.463 mmol) in dichloromethane (3 mL) was added triethylamine (303 mg, 3 mmol). The mixture was stirred at room temperature overnight. The mixture was concentrated and the residue was purified by chromatography on silica gel (CH2Cl2/CH3OH=10:1) to give the title compound (0.4 g, 78% yield). MS (ESI) m/z 421 (M+H)+. The mixture was concentrated the residue was purified by chromatography on silica gel (CH2Cl2/CH3OH=10:1)

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To (7S,8aR)-2-benzyloctahydropyrrolo[1,2-a]pyrazin-7-ol (Example 17D, 5 g, 21.52 mmol) and solvent 2,2,2-trifluoroethanol (50 mL) were added to 20% palladium hydroxide on carbon, wet (0.500 g) in a pressure bottle. The mixture was stirred at 50° C. for 16 hours under 30 psi of hydrogen. The mixture was filtered through a nylon membrane to give a crude (7S,8aR)-octahydropyrrolo[1,2-a]pyrazin-7-ol. To a solution of the above crude (7S,8aR)-octahydropyrrolo[1,2-a]pyrazin-7-ol (1.0 g, 7 mmol) and triethylamine (1.13 g, 11.2 mmol) in dichloromethane (40 mL) was slowly added a solution of 3-(trifluoromethyl)benzene-1-sulfonyl chloride (1.712 g, 7 mmol) in dichloromethane (2 mL). The solution was stirred at room temperature for 4 hours. The solution was concentrated, diluted with ethyl acetate (100 mL), washed with water (20 mL), dried over sodium sulfate, filtered, and concentrated. The residue was purified by chromatography on silica gel (dichloromethane/methanol=10:1) to give the title compound. 1H NMR (400 MHz, DMSO-d6) δ ppm 1.43-1.58 (m, 2H), 1.97 (m, 2H), 2.10-2.35 (m, 3H), 2.90 (m, 1H), 3.20 (m, 1H), 3.62 (m, 1H), 3.77 (m, 1H), 4.14 (m, 1H), 4.80 (m, 1H), 7.92 (m, 2H), 8.10 (m, 2H); MS (ESI) m/z 351 (M+H)+. The solution was concentrated diluted with ethyl acetate (100 mL) washed with water (20 mL) dried over sodium sulfate filtered concentrated The residue was purified by chromatography on silica gel (dichloromethane/methanol=10:1)

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To (7S,8aR)-2-benzyloctahydropyrrolo[1,2-a]pyrazin-7-ol (Example 17D, 5 g, 21.52 mmol) and solvent 2,2,2-trifluoroethanol (50 mL) were added to 20% palladium hydroxide on carbon, wet (0.500 g) in a pressure bottle. The mixture was stirred at 50° C. for 16 hours under 30 psi of hydrogen. The mixture was filtered through a nylon membrane to give a crude (7S,8aR)-octahydropyrrolo[1,2-a]pyrazin-7-ol. To a solution of the above crude (7S,8aR)-octahydropyrrolo[1,2-a]pyrazin-7-ol (1.0 g, 7 mmol) and triethylamine (1.13 g, 11.2 mmol) in dichloromethane (40 mL) was slowly added a solution of 3-(trifluoromethyl)benzene-1-sulfonyl chloride (1.712 g, 7 mmol) in dichloromethane (2 mL). The solution was stirred at room temperature for 4 hours. The solution was concentrated, diluted with ethyl acetate (100 mL), washed with water (20 mL), dried over sodium sulfate, filtered, and concentrated. The residue was purified by chromatography on silica gel (dichloromethane/methanol=10:1) to give the title compound. 1H NMR (400 MHz, DMSO-d6) δ ppm 1.43-1.58 (m, 2H), 1.97 (m, 2H), 2.10-2.35 (m, 3H), 2.90 (m, 1H), 3.20 (m, 1H), 3.62 (m, 1H), 3.77 (m, 1H), 4.14 (m, 1H), 4.80 (m, 1H), 7.92 (m, 2H), 8.10 (m, 2H); MS (ESI) m/z 351 (M+H)+. The mixture was filtered through a nylon membrane

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To (7S,8aR)-octahydropyrrolo[1,2-a]pyrazin-7-ol (0.208 g, 1.463 mmol) and 4-(trifluoromethyl)benzene-1-sulfonyl chloride (0.358 g, 1.463 mmol) in dichloromethane (3 mL) was added triethylamine (303 mg, 3 mmol). The mixture was stirred at room temperature overnight. The mixture was concentrated and the residue was purified by chromatography on silica gel (CH2Cl2/CH3OH=10:1) to give the title compound (0.4 g, 78% yield). MS (ESI) m/z 421 (M+H)+. The mixture was concentrated the residue was purified by chromatography on silica gel (CH2Cl2/CH3OH=10:1)

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To (7S,8aR)-2-benzyloctahydropyrrolo[1,2-a]pyrazin-7-ol (Example 17D, 5 g, 21.52 mmol) and solvent 2,2,2-trifluoroethanol (50 mL) were added to 20% palladium hydroxide on carbon, wet (0.500 g) in a pressure bottle. The mixture was stirred at 50° C. for 16 hours under 30 psi of hydrogen. The mixture was filtered through a nylon membrane to give a crude (7S,8aR)-octahydropyrrolo[1,2-a]pyrazin-7-ol. To a solution of the above crude (7S,8aR)-octahydropyrrolo[1,2-a]pyrazin-7-ol (1.0 g, 7 mmol) and triethylamine (1.13 g, 11.2 mmol) in dichloromethane (40 mL) was slowly added a solution of 3-(trifluoromethyl)benzene-1-sulfonyl chloride (1.712 g, 7 mmol) in dichloromethane (2 mL). The solution was stirred at room temperature for 4 hours. The solution was concentrated, diluted with ethyl acetate (100 mL), washed with water (20 mL), dried over sodium sulfate, filtered, and concentrated. The residue was purified by chromatography on silica gel (dichloromethane/methanol=10:1) to give the title compound. 1H NMR (400 MHz, DMSO-d6) δ ppm 1.43-1.58 (m, 2H), 1.97 (m, 2H), 2.10-2.35 (m, 3H), 2.90 (m, 1H), 3.20 (m, 1H), 3.62 (m, 1H), 3.77 (m, 1H), 4.14 (m, 1H), 4.80 (m, 1H), 7.92 (m, 2H), 8.10 (m, 2H); MS (ESI) m/z 351 (M+H)+. The solution was concentrated diluted with ethyl acetate (100 mL) washed with water (20 mL) dried over sodium sulfate filtered concentrated The residue was purified by chromatography on silica gel (dichloromethane/methanol=10:1)

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To (7S,8aR)-2-benzyloctahydropyrrolo[1,2-a]pyrazin-7-ol (Example 17D, 5 g, 21.52 mmol) and solvent 2,2,2-trifluoroethanol (50 mL) were added to 20% palladium hydroxide on carbon, wet (0.500 g) in a pressure bottle. The mixture was stirred at 50° C. for 16 hours under 30 psi of hydrogen. The mixture was filtered through a nylon membrane to give a crude (7S,8aR)-octahydropyrrolo[1,2-a]pyrazin-7-ol. To a solution of the above crude (7S,8aR)-octahydropyrrolo[1,2-a]pyrazin-7-ol (1.0 g, 7 mmol) and triethylamine (1.13 g, 11.2 mmol) in dichloromethane (40 mL) was slowly added a solution of 3-(trifluoromethyl)benzene-1-sulfonyl chloride (1.712 g, 7 mmol) in dichloromethane (2 mL). The solution was stirred at room temperature for 4 hours. The solution was concentrated, diluted with ethyl acetate (100 mL), washed with water (20 mL), dried over sodium sulfate, filtered, and concentrated. The residue was purified by chromatography on silica gel (dichloromethane/methanol=10:1) to give the title compound. 1H NMR (400 MHz, DMSO-d6) δ ppm 1.43-1.58 (m, 2H), 1.97 (m, 2H), 2.10-2.35 (m, 3H), 2.90 (m, 1H), 3.20 (m, 1H), 3.62 (m, 1H), 3.77 (m, 1H), 4.14 (m, 1H), 4.80 (m, 1H), 7.92 (m, 2H), 8.10 (m, 2H); MS (ESI) m/z 351 (M+H)+. The mixture was filtered through a nylon membrane

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A mixture of (7S,8aR)-2-benzyloctahydropyrrolo[1,2-a]pyrazin-7-ol (Example 65D, 5 g, 21.52 mmol) and 2,2,2-trifluoroethanol (50 mL) was added to 20% palladium hydroxide on carbon, wet (0.500 g) in a pressure bottle. The mixture was stirred at 50° C. for 16 hours under 30 psi of hydrogen. The mixture was filtered through a nylon membrane to give a crude intermediate (7S,8aR)-octahydropyrrolo[1,2-a]pyrazin-7-ol. The title compound was prepared according to the procedure described in Example 61 substituting (7S,8aR)-octahydropyrrolo[1,2-a]pyrazin-7-ol for (7R,8aS)-octahydropyrrolo[1,2-a]pyrazin-7-ol. 1H NMR (400 MHz, DMSO-d6) δ ppm 1.43-1.63 (m, 2H), 2.10-2.27 (m, 3H), 2.50 (m, 1H), 2.80-3.00 (m, 2H), 3.20-3.50 (m, 2H), 4.22 (m, 1H), 4.42-4.60 (m, 1H), 4.80 (m, 1H), 7.70 (m, 3H), 7.82 (m, 1H); MS (ESI) m/z 315 (M+H)+. The mixture was filtered through a nylon membrane

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To (7S,8aR)-octahydropyrrolo[1,2-a]pyrazin-7-ol (0.208 g, 1.463 mmol) and 4-(trifluoromethyl)benzene-1-sulfonyl chloride (0.358 g, 1.463 mmol) in dichloromethane (3 mL) was added triethylamine (303 mg, 3 mmol). The mixture was stirred at room temperature overnight. The mixture was concentrated and the residue was purified by chromatography on silica gel (CH2Cl2/CH3OH=10:1) to give the title compound (0.4 g, 78% yield). MS (ESI) m/z 421 (M+H)+. The mixture was concentrated the residue was purified by chromatography on silica gel (CH2Cl2/CH3OH=10:1)

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To (7S,8aR)-2-benzyloctahydropyrrolo[1,2-a]pyrazin-7-ol (Example 17D, 5 g, 21.52 mmol) and solvent 2,2,2-trifluoroethanol (50 mL) were added to 20% palladium hydroxide on carbon, wet (0.500 g) in a pressure bottle. The mixture was stirred at 50° C. for 16 hours under 30 psi of hydrogen. The mixture was filtered through a nylon membrane to give a crude (7S,8aR)-octahydropyrrolo[1,2-a]pyrazin-7-ol. To a solution of the above crude (7S,8aR)-octahydropyrrolo[1,2-a]pyrazin-7-ol (1.0 g, 7 mmol) and triethylamine (1.13 g, 11.2 mmol) in dichloromethane (40 mL) was slowly added a solution of 3-(trifluoromethyl)benzene-1-sulfonyl chloride (1.712 g, 7 mmol) in dichloromethane (2 mL). The solution was stirred at room temperature for 4 hours. The solution was concentrated, diluted with ethyl acetate (100 mL), washed with water (20 mL), dried over sodium sulfate, filtered, and concentrated. The residue was purified by chromatography on silica gel (dichloromethane/methanol=10:1) to give the title compound. 1H NMR (400 MHz, DMSO-d6) δ ppm 1.43-1.58 (m, 2H), 1.97 (m, 2H), 2.10-2.35 (m, 3H), 2.90 (m, 1H), 3.20 (m, 1H), 3.62 (m, 1H), 3.77 (m, 1H), 4.14 (m, 1H), 4.80 (m, 1H), 7.92 (m, 2H), 8.10 (m, 2H); MS (ESI) m/z 351 (M+H)+. The solution was concentrated diluted with ethyl acetate (100 mL) washed with water (20 mL) dried over sodium sulfate filtered concentrated The residue was purified by chromatography on silica gel (dichloromethane/methanol=10:1)

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To (7S,8aR)-2-benzyloctahydropyrrolo[1,2-a]pyrazin-7-ol (Example 17D, 5 g, 21.52 mmol) and solvent 2,2,2-trifluoroethanol (50 mL) were added to 20% palladium hydroxide on carbon, wet (0.500 g) in a pressure bottle. The mixture was stirred at 50° C. for 16 hours under 30 psi of hydrogen. The mixture was filtered through a nylon membrane to give a crude (7S,8aR)-octahydropyrrolo[1,2-a]pyrazin-7-ol. To a solution of the above crude (7S,8aR)-octahydropyrrolo[1,2-a]pyrazin-7-ol (1.0 g, 7 mmol) and triethylamine (1.13 g, 11.2 mmol) in dichloromethane (40 mL) was slowly added a solution of 3-(trifluoromethyl)benzene-1-sulfonyl chloride (1.712 g, 7 mmol) in dichloromethane (2 mL). The solution was stirred at room temperature for 4 hours. The solution was concentrated, diluted with ethyl acetate (100 mL), washed with water (20 mL), dried over sodium sulfate, filtered, and concentrated. The residue was purified by chromatography on silica gel (dichloromethane/methanol=10:1) to give the title compound. 1H NMR (400 MHz, DMSO-d6) δ ppm 1.43-1.58 (m, 2H), 1.97 (m, 2H), 2.10-2.35 (m, 3H), 2.90 (m, 1H), 3.20 (m, 1H), 3.62 (m, 1H), 3.77 (m, 1H), 4.14 (m, 1H), 4.80 (m, 1H), 7.92 (m, 2H), 8.10 (m, 2H); MS (ESI) m/z 351 (M+H)+. The mixture was filtered through a nylon membrane